This project is designed to investigate neuropathological correlates of affective disorders using paradigms in which event-related potential (ERP) and reaction time (RT) measures are concurrently obtained. We have collected ERP and clinical data on over 50 inpatients meeting research diagnostic criteria for depression and age-matched controls. Eleven of these patients have been tested after drug washout and after a course of anti-depressant therapy. An additional 13 patients have been tested after drug washout only. The remaining patients have been tested while medicated. Amplitude of the N1 component of the ERP showed significantly less increase to increases in intensity of auditory stimuli in depressed than control subjects. The effects of manipulating attention towards and away from stimuli remain to be analyzed. The late-positive component of the ERP, the P3, elicited in an auditory choice RT task, was smaller and later in depressed than control patients. The contribution of latency variability to reduced amplitude will be assessed as will the effect of sequential probability; analysis of the relationship between P3 latency and RT in individual trials will be performed. Data from a visual analog of the auditory choice RT task have yet to be analyzed. During the final year of the project, additional patients, selected to provide a sample representing the full range of symptom severity and diagnostic subtypes, will be added. ERP analysis will be completed and correlational analysis of the relationship between ERPs and clinical variables performed. The effect of drugs, both cross-sectionally and longitudinally, will be evaluated.